tbuckley/cabot-search huggingface dataset:
US Food and Drug Administration Review Time of Supplemental New Indication Approvals of Drugs and Biologics, 2017 to 2019
Authors: Meera M. Dhodapkar, Joseph S. Ross, Reshma Ramachandran
Journal: JAMA Network Open (2023)

This cross-sectional study examines US Food and Drug Administration regulatory review time of supplemental new indication approvals of drugs and biologics between 2017 and 2019.
Racial and Ethnic Differences in Encounters Related to Suicidal Behavior Among Children and Adolescents With Medicaid Coverage During the COVID-19 Pandemic
Authors: Mir M. Ali, Kristina D. West, Joel Dubenitz, Pamela End of Horn, David Paschane, Sarah A. Lieff
Journal: JAMA Pediatrics (2023)

This cohort study evaluates rates of encounters for suicidal behavior by race and ethnicity among children with Medicaid coverage during vs before the COVID-10 pandemic.
Classification of accelerated phase chronic myeloid leukemia in the era of the <scp>BCR</scp>::<scp>ABL1</scp> tyrosine kinase inhibitors: A work in progress
Authors: Hagop M. Kantarjian, Ayalew Tefferi
Journal: American Journal of Hematology (2023)

Hagop Kantarjian: Research grants from Novartis, BMS, Takeda, Ascentage Pharma. Ayalew Tefferi: none. Data sharing is not applicable to this article.
Epidemiology of clinically significant forms of alpha‐ and <scp>beta‐thalassemia</scp>: A global map of evidence and gaps
Authors: Khaled M. Musallam, Louise Lombard, Kristin D. Kistler, Maria Arregui, Keely S. Gilroy, Christina Chamberlain, Erin Zagadailov, Kimberly Ruiz, Ali T. Taher
Journal: American Journal of Hematology (2023)

Abstract This systematic literature review assessed the global prevalence and birth prevalence of clinically significant forms of alpha‐ and beta‐thalassemia. Embase, MEDLINE, and the Cochrane Library were searched for observational studies published January 1, 2000, to September 21, 2021. Of 2093 unique records identified, 69 studies reported across 70 publications met eligibility criteria, including 6 records identified from bibliography searches. Thalassemia prevalence estimates varied across countries and even within countries. Across 23 population‐based studies reporting clinically significant alpha‐thalassemia (e.g., hemoglobin H disease and hemoglobin Bart's hydrops fetalis) and/or beta‐thalassemia (beta‐thalassemia intermedia, major, and/or hemoglobin E/beta‐thalassemia), prevalence estimates per 100 000 people ranged from 0.2 in Spain (over 2014–2017) to 27.2 in Greece (2010–2015) for combined beta‐ plus alpha‐thalassemia; from 0.03 in Spain (2014–2017) to 4.5 in Malaysia (2007–2018) for alpha‐thalassemia; and from 0.2 in Spain (2014–2017) to 35.7 to 49.6 in Iraq (2003–2018) for beta‐thalassemia. Overall, the estimated prevalence of thalassemia followed the predicted pattern of being higher in the Middle East, Asia, and Mediterranean than in Europe or North America. However, population‐based prevalence estimates were not found for many countries, and there was heterogeneity in case definitions, diagnostic methodology, type of thalassemia reported, and details on transfusion requirements. Limited population‐based birth prevalence data were found. Twenty‐seven studies reported thalassemia prevalence from non–population‐based samples. Results from such studies likely do not have countrywide generalizability as they tended to be from highly specific groups. To fully understand the global prevalence of thalassemia, up‐to‐date, population‐based epidemiological data are needed for many countries.
NPM1 mutation reprograms leukemic transcription network via reshaping TAD topology
Authors: Qian Lai, Karina Hamamoto, Huacheng Luo, Zachary Zaroogian, Caixian Zhou, Julia Lesperance, Jie Zha, Yi Qiu, Olga A. Guryanova, Suming Huang, Bing Xu
Journal: Leukemia (2023)

C-terminal mutation of Nucleophosmin 1 (NPM1C+) was thought to be a primary driving event in acute myeloid leukemia (AML) that reprograms leukemic-associated transcription programs to transform hematopoietic stem and progenitor cells (HSPCs). However, molecular mechanisms underlying NPM1C+-driven leukemogenesis remain elusive. Here, we report that NPM1C+ activates signature HOX genes and reprograms cell cycle regulators by altering CTCF-driven topologically associated domains (TADs). Hematopoietic-specific NPM1C+ knock-in alters TAD topology leading to disrupted regulation of the cell cycle as well as aberrant chromatin accessibility and homeotic gene expression, which results in myeloid differentiation block. Restoration of NPM1 within the nucleus re-establishes differentiation programs by reorganizing TADs critical for myeloid TFs and cell cycle regulators that switch the oncogenic MIZ1/MYC regulatory axis in favor of interacting with coactivator NPM1/p300, and prevents NPM1C+-driven leukemogenesis. In sum, our data reveal that NPM1C+ reshapes CTCF-defined TAD topology to reprogram signature leukemic transcription programs required for cell cycle progression and leukemic transformation.
BH01 Experiences of nail pathology seen within a specialist clinic over 1 year
Authors: Charlotte Wolfe, Christina Ye, Ling Li, Daniel Yiu, Dhruvkumar Laheru
Journal: British Journal of Dermatology (2023)

Abstract Nail disorders comprise an important subset of dermatological conditions that can pose diagnostic and therapeutic challenges for clinicians. The pathology can be limited to the nail or reflect wider systemic processes. We present a single-centre cross-sectional study on nail conditions seen within a specialist nail clinic over a 12-month period. Demographic and clinical data were collected retrospectively using electronic patient records and analysed using a coding framework. In total, 62 new patients, including 12 paediatric patients, were seen between August 2021 and July 2022. The average patient age was 41 years. Only four patients were seen twice. In terms of ethnicity, 28 patients were White, six were Asian, two were Black and one patient was of mixed race. Ethnicity data were unavailable for 25 patients. Although most patients presented with a single pathology (76%), 24% presented with two or more pathologies. In total, 79 nail diagnoses were given for 62 patients; aetiological categories included infection (onychomycosis, infection other), inflammatory, tumour, trauma, melanonychia, congenital, structural, systemic and idiopathic. Patients had fingernail involvement alone, toenail involvement alone or involvement of both sites. The most common pathologies seen were infection (other) and infection (onychomycosis), accounting for 33% of the conditions seen; melanonychia was next most frequently observed at 18%. Onychomycosis accounts for up to 40% of all nail diseases in the UK. In our nail clinic, onychomycosis consisted of 17.7% of diagnoses. Across Europe, the overall prevalence has been reported to be 23%. In France, the prevalence of onychomycosis is reported to be 20–30% within general practice and dermatology. The true incidence is difficult to assess due to the lack of large-scale studies. We may see fewer cases in secondary care due to the podiatry service available in the UK. The availability of podiatry professionals varies across the world and we believe this plays a role in the presentation of nail diseases to physician-led clinics. Our review here did not encompass UK 2-week-wait cancer referrals, which were accommodated with our consultant as soon as possible. Patients often present to our clinic due to diagnostic uncertainty, especially regarding linear melanonychia, which generates anxiety in primary care. Secondary complications such as nail dystrophy and toenail displacement are also frequent causes for referral. This review, although single centre and retrospective, is a comprehensive snapshot of nail pathology at a UK specialist centre and demonstrates the pathologies encountered in secondary care, helping to plan future services and direct both primary care and trainee teaching.
PS06 The beast beneath the blisters: assessment of depression and anxiety in patients with immunobullous disorders in a tertiary referral centre
Authors: Sarah Ryan, Eunice Lee, Hamisha Salih, Jenny Radcliffe, Claudia DeGiovanni
Journal: British Journal of Dermatology (2023)

Abstract Immunobullous diseases can be disabling in the acute phase, causing widespread painful or pruritic skin and mucosal lesions. The subsequent psychological consequences of these disorders have not been fully evaluated. We treated a 53-year-old woman for severe bullous pemphigoid affecting her skin and oral mucosa. Following resolution of disease, she was left with debilitating anxiety and depression. This case prompted us to look at the psychological impact of immunobullous disease in our cohort. We used the Patient Health Questionnaire (PHQ-9), General Anxiety Disorder (GAD-7) and Dermatology Life Quality Index to establish the psychosocial impact in patients attending the immunobullous specialist clinic at a large tertiary dermatology centre. An assessment of pain using a numerical pain-rating scale and a question regarding any pre-existing mental health conditions were included. Twelve patients with various immunobullous conditions were surveyed. Seventy-five per cent (n = 9) of patients were identified as having a mood disorder via their PHQ-9 and GAD-7 scores. The PHQ-9 scores indicated mild (50%), moderate (17%) and severe (8%) depression symptoms in these patients. Twenty-five per cent and 17% of patients had a GAD-7 score indicating mild and moderate anxiety, respectively. Three patients declared that they had a previous mental health diagnosis; however, only mild depression and mild anxiety were identified in two of these patients. Only one of these patients volunteered mental health symptoms during their consultation, indicating an unrecognized burden of disease in this community. Our findings support previous research indicating high rates of depression in patients with immunobullous disease. Furthermore, there is an established association between bullous pemphigoid and neuropsychiatric conditions, with identification of autoantigen expression in the central nervous system. Mood disorders have a significant effect on patients’ experience of disease, and are likely to have an impact on disease course and engagement with treatment. A large European study found that dermatologists underestimate the severity of mood disorders. Therefore, the incorporation of validated measures for assessment of mood disorders such as PHQ-9 and GAD-7 into clinical practice is essential to identify the high proportion of patients with immunobullous disease suffering from these disorders. Quality of life measures, which are commonly assessed, are not sufficient for holistic management of these patients. These findings support the invaluable role of a psychologist within dermatology centres, and appropriate referrals to these services will improve with assessment during clinic consultations.
P98 Real-world effectiveness of guselkumab in absolute Psoriasis Area and Severity Index-stratified patients with psoriasis: data from the British Association of Dermatologists Biologics and Immunomodulators Register
Authors: Faraz Ali, Xiayi Wang, Justin Gillespie, Louise M Topping
Journal: British Journal of Dermatology (2023)

Abstract Guselkumab is a fully human monoclonal antibody that inhibits interleukin-23 by selectively targeting the p19 subunit. Long-term evaluations have demonstrated high levels of clinical response and improvement in patient-reported outcomes over 5 years of guselkumab treatment in patients with psoriasis. Psoriasis has a significant and negative impact on a patient’s quality of life, even among patients with a Psoriasis Area and Severity Index (PASI) score &amp;lt; 10. Both absolute PASI (aPASI) and the Dermatology Life Quality Index (DLQI) are widely used tools to assess disease impact, as well as treatment eligibility and response. This retrospective analysis evaluated the impact of guselkumab treatment over 1 year across aPASI-stratified patients with psoriasis in BADBIR, a national pharmacovigilance registry documenting longitudinal clinical data for individuals with psoriasis initiating systemic therapies. Retrospective analyses of the guselkumab cohort were carried out using BADBIR data collected up to September 2021. Data were analysed for patients who had initiated guselkumab treatment and had recorded aPASI and DLQI assessments at both baseline and the 12-month follow-up. Patients were stratified according to psoriasis severity at baseline: aPASI &amp;lt; 5, aPASI ≥ 5 to ≤ 10 and aPASI &amp;gt; 10 disease. Treatment effect was defined as the mean improvement in DLQI and aPASI scores for the overall group of guselkumab-treated patients and for subsets of patients with aPASI &amp;lt; 5, aPASI ≥ 5 to ≤ 10 and aPASI &amp;gt; 10 at baseline. Five patients were excluded owing to treatment cessation prior to the 12-month cutoff. Following 12 months of guselkumab treatment, patients with aPASI &amp;lt; 5, aPASI ≥ 5 to ≤ 10 and aPASI &amp;gt; 10 at baseline achieved a mean (SD) DLQI score of 2.18 (5.64), 2.79 (5.15) and 1.80 (3.56), representing a decrease of 62.0%, 74.8% and 89.1% from baseline, respectively. Additionally, patients with aPASI &amp;lt; 5, aPASI ≥ 5 to ≤ 10 and aPASI &amp;gt; 10 at baseline achieved a mean (SD) aPASI score of 0.96 (1.84), 3.16 (3.90) and 2.78 (4.93), representing a decrease of 40%, 58.6% and 84.5% from baseline, respectively. Among patients with an aPASI score &amp;lt; 10 at baseline (n = 53), 83.0% (n = 44) achieved aPASI score ≤ 3; of these, 67.9% (n = 36) achieved an aPASI score ≤ 2 and 54.7% (n = 29) achieved an aPASI score ≤ 1. These data demonstrate that guselkumab produces an effective and consistent response in patients with a broad range of disease severity at baseline, as reflected by mean improvements in aPASI and DLQI. Greater reductions in DLQI and aPASI scores were observed after 12 months of guselkumab treatment in patients with more severe psoriasis at baseline.
PA25 Persistent and widespread infantile transient smooth muscle contraction of the skin: an atypical presentation of a rare condition.
Authors: Elizabeth Keeling, Clare Devereux, Fiona Browne
Journal: British Journal of Dermatology (2023)

Abstract Infantile transient smooth muscle contraction of the skin is a rare entity. Eleven cases have been described in the literature to date. Herein, we describe an unusual presentation, persistent and widespread in nature. A 2-year-old girl presented with asymptomatic bilateral transient textural change of the skin overlying the thighs. Textural changes were noted from birth, occurring a number of times each day. Episodes resolved spontaneously, sometimes within minutes, on occasion lasting up to 1 h. The child remained systemically well during episodes. Textural change progressed to involve the skin overlying the abdomen. Friction and temperature change did not provoke episodes. No other triggers were elicited. Background history included metatarsus adductus, which was under routine follow-up with orthopaedics. Full skin examination between episodes revealed no cutaneous abnormality. The areas affected were normal to palpate. Photographs and videos of episodes revealed marked textural change of the skin overlying both thighs and abdomen, with a striking stippled appearance. Laboratory investigations, including tryptase, lactate dehydrogenase, immunoglobulins and complement, were unremarkable. A case series first described nine cases of infantile transient smooth muscle contraction in 2013 (Torrelo A, Moreno S, Castro C et al. Infantile transient smooth muscle contraction of the skin. J Am Acad Dermatol 2013; 69:498–500). Textural skin changes occurred most frequently on the lower limbs. In eight of these cases, episodes resolved within 1 min. Episodes occurred both spontaneously and secondary to light friction from clothing, cool air and bathing. The majority of cases were noted from birth or in the first days of life. Skin biopsies taken from three of these patients revealed no abnormality. Episodes resolved by 2 years of age in all cases. It has been suggested that this transient phenomenon may be secondary to autonomic nervous system immaturity, primitive reflex phenomena or transient hypersensitivity of the smooth muscle. A more recent case has since been described in the literature (Theodosiou G, Belfrage E, Berggård K, Cristiansen J. Infantile transient smooth muscle contraction of the skin: a case report and literature review. Eur J Dermatol 2021; 31:260–1). We describe a persistent case of infantile transient smooth muscle contraction of the skin, in a child aged &amp;gt; 2 years, with prolonged episodes, progressing from lower limbs to truncal involvement. Recognition of this rare condition is important, to allow appropriate reassurance regarding its benign and self-limiting nature.
P78 Amyopathic dermatomyositis: a retrospective review of 21 cases
Authors: Pavan Sambi, Wajeeha Khan, Phil Laws
Journal: British Journal of Dermatology (2023)

Abstract Amyopathic dermatomyositis (ADM) is a clinical subtype of dermatomyositis, which can be associated with malignancy and lung disease. We report a retrospective review of 21 cases of ADM presenting to a tertiary clinic. We discuss the clinical presentations, investigation, and cancer and lung associations. Patients were included if they met the European League Against Rheumatism (EULAR)/American College of Rheumatology (ACR) criteria for ADM. We identified 21 patients with ADM (16 women and five men). Mean age at diagnosis was 61 years (range 35–81). Clinical features were as follows: Gottron papules (n = 15; 71%), nailfold involvement (n = 16; 76%), heliotrope rash (n = 12; 57%), shawl sign (n = 11; 52%), Raynaud phenomenon (n = 9; 43%), scalp disease (n = 6; 29%) and calcinosis (n = 3; 14%). Antinuclear antibody (ANA) was positive in 76% of patients (n = 16) and 41% (n = 9) had myositis-specific antibodies. Four patients had a prediagnosed malignancy. One patient had prostate cancer detected on malignancy screen. One nerve sheath tumour was diagnosed within 1 year of ADM diagnosis and one cholangiocarcinoma within 3 years. Three patients were found to have mild lung fibrosis, but none was found to have severe interstitial lung disease. Patients were treated with corticosteroids (n = 16), hydroxychloroquine (n = 11), metho­trexate (n = 10), mycophenolate (n = 6), cyclophosphamide (n = 3), rituximab (n = 3), intravenous immunoglobulin (n = 3), mepacrine (n = 2), azathioprine (n = 1), ciclosporin (n = 1) and thalidomide (n = 1). In conclusion, in our study, a female preponderance and cutaneous findings involving extremities were seen in the majority of patients (95%), in keeping with other published data (el-Azhary RA, Pakzad SY. Amyopathic dermatomyositis: retrospective review of 37 cases. J Am Acad Dermatol 2002; 46:560–5). Our study further highlights the heterogeneity of cutaneous clinical presentation of ADM, which is broadly consistent with other reported cohorts [el-Azhary and Pakzad; Tang K, Zhang H, Jin H. Clinical characteristics and management of patients with clinical amyopathic dermatomyositis: a retrospective study of 64 patients at a tertiary dermatology department. Front Med (Lausanne) 2021; 8:783416]. We report high levels of hand and nail involvement, emphasizing the need for formal assessment of hands, including dermoscopy of nails. ANA was positive in 76% of patients; other reported data suggest that it is positive in 31.6–71% (el-Azhary and Pakzad; Tang et al.). Although previous studies have found myositis-specific antibodies in 87.5% (Tang et al.), only 42% in our cohort had positive antibodies; therefore, a high index of suspicion is required to detect cases and appropriately screen for associated morbidity (lung disease and malignancy). In addition, a third of patients had associated malignancy prediagnosed or within 3 years of diagnosis, highlighting the importance of baseline screening and ongoing follow-up.
PS12 A new meaning to ‘picking your nose’: the use of <i>N</i>-acetylcysteine to treat trigeminal trophic syndrome
Authors: Emily Vaughan, Maaz Abid, Rabi Nambi, Rand Hawari
Journal: British Journal of Dermatology (2023)

Abstract Trigeminal trophic syndrome (TTS) is a rare condition in which patients induce unilateral facial ulceration by persistent physical manipulation. Peripheral or central damage to the trigeminal nerve causes anaesthesia, paraesthesia, formication or pruritus. Compulsive skin picking leads to ulceration of the ala nasi, cheek, scalp or mouth in the distribution of the trigeminal nerve. Patients with TTS are often subjected to extensive investigations and can be misdiagnosed as having a psychocutaneous disorder, such as dermatitis artefacta, skin-picking disorder or delusional parasitosis. We describe a 90-year-old woman who developed TTS following rhizotomy and radiofrequency treatment for trigeminal neuralgia. Underlying infectious, malignant and vasculitic causes for her ala nasi and cheek ulceration were ruled out through six incisional biopsies and two punch biopsies over 8 years. Previous treatment of TTS has included patient education and physical barriers (e.g. face masks and occlusive dressings). Treatment to date has been challenging, with trials of medications to address paraesthesia, including carbamazepine, gabapentin and amitriptyline. This patient re-presented to dermatology in 2022 with significantly worsened ulceration to her cheek and severe loss of nasal cartilage. In September 2022, the patient was started on N-acetylcysteine (NAC) 600 mg twice daily, and within 3 months, there was a considerable improvement. This drug is a mucolytic that has historically been used as an antidote for paracetamol overdose. It has antioxidant properties by replenishing glutathione and maintaining redox balance within cells. It also modulates neurotransmitters and can increase glutamate and alter dopamine levels. In addition, it has anti-inflammatory action by inhibiting interleukins (ILs), including IL-6 (Adil M, Amin SS. N-acetylcysteine in dermatology. Indian J Dermatol Venereol Leprol 2018; 84:652). In recent years, NAC has been reported to be successful in small case series and case reports among patients with trichotillomania, skin-picking disorders, onychotillomania, toxic epidermal necrolysis, alopecia, contact dermatitis, atopic dermatitis and wound healing (Grant JE, Chamberlain SR, Redden SA, Leppink EW. N-Acetylcysteine in the treatment of excoriation disorder. JAMA Psychiatry 2016; 73:490). It is an inexpensive drug that appears to be well tolerated and effective. To our knowledge, this is the first case report of the use of NAC in TTS. In summary, this was a case of TTS in a 90-year-old woman who successfully responded to NAC. The drug has antioxidant, anti-inflammatory and neurotransmitter modulatory effects. Reliable randomized controlled studies are needed to confirm the efficacy and optimum dose of NAC. Increased awareness of this rare syndrome and potential treatment options will ensure prompt diagnosis and prevention of permanent disfiguration.